Figure 1.

MiR-22 directly inhibits TET2 expression, resulting in hypermethylation and decreased expression of TET2 target genes such as AIM2 and SP140. AIM2 has a role in the reduction of cell proliferation by inducing cell cycle arrest, and along with SP140, plays a crucial role in MDS development and leukemogenesis. Additionally, miR-22 downregulates PTEN expression, a phosphatase that dephosphorylates phosphatidylinositol-3,4,5-trisphosphate (PIP3), thereby counteracting the activation of the PI3K/AKT pathway, which leads to aberrant hematopoiesis. The concomitant silencing of TET2 and PTEN by miR-22 enhances cell proliferation and survival, ultimately contributing to the development of MDS and leukemogenesis (14).